Phosphoinositide-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway inhibitors are a novel class of antineoplastic agent available for the treatment of various cancers. With improved cancer outcomes and survival, individuals are exposed to these antineoplastic therapies for longer periods of time and therefore, the consideration of adverse effects is of increasing importance. The PI3K/Akt/mTOR signaling pathway plays a critical role in regulating cellular processes such as growth and proliferation, but also regulates the metabolic effects of insulin such as glucose uptake and glycogen synthesis. Therefore, hyperglycemia and insulin resistance are frequently reported adverse effects. There are no recent consensus guidelines on the management of hyperglycemia secondary to PI3K/Akt/mTOR inhibitors, with the latest guidelines produced in 2012 – when many of these agents were still undergoing development. As we now have a greater understanding of the underlying mechanisms and patterns in which hyperglycemia is induced and access to an increasing array of glucose-lowering agents, an update of the previous guidelines accommodating these understandings and developments is timely. This review will provide a comprehensive summary of the current literature with regards to the incidence of hyperglycemia associated with each agent, as well as the different pathways and mechanisms in which hyperglycemia is induced. Our proposed up-to-date strategy for the specific management of PI3K/Akt/mTOR inhibitor-induced hyperglycemia will also aim to facilitate management of this complex oncological population.

Phosphoinositide-3-kinase/Akt/哺乳动物雷帕霉素靶点 (PI3K/Akt/mTOR) 通路抑制剂是一类可用于治疗各种癌症的新型抗肿瘤药物。随着癌症结果和生存率的提高，个体暴露于这些抗肿瘤疗法的时间更长，因此，考虑不良反应变得越来越重要。PI3K/Akt/mTOR 信号通路在调节细胞过程（如生长和增殖）中发挥关键作用，同时也调节胰岛素的代谢作用，如葡萄糖摄取和糖原合成。因此，高血糖和胰岛素抵抗经常被报道为不良反应。最近没有关于继发于 PI3K/Akt/mTOR 抑制剂的高血糖管理的共识指南，与 2012 年制定的最新指南相结合——当时其中许多药物仍在开发中。由于我们现在对诱发高血糖的潜在机制和模式有了更深入的了解，并且可以使用越来越多的降糖药物，因此更新之前的指南以适应这些理解和发展是及时的。本综述将全面总结当前文献中与每种药物相关的高血糖发生率，以及诱发高血糖的不同途径和机制。我们提出的针对 PI3K/Akt/mTOR 抑制剂诱导的高血糖症的具体管理的最新策略也将旨在促进对这一复杂肿瘤人群的管理。